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推进儿童多发性硬化症的治疗:B细胞靶向疗法的前景

Advancing Treatment in Pediatric Multiple Sclerosis: The Promise of B-Cell-Targeting Therapies.

作者信息

Skarlis Charalampos, Kotsari Maria, Anagnostouli Maria

机构信息

Research Immunogenetics Laboratory, First Department of Neurology, School of Medicine, National and Kapodistrian University of Athens, Aeginition University Hospital, Vas. Sofias 72-74, 11528 Athens, Greece.

Multiple Sclerosis and Demyelinating Diseases Unit, Center of Expertise for Rare Demyelinating and Autoimmune Diseases of CNS, First Department of Neurology, School of Medicine, National and Kapodistrian University of Athens, Aeginition University Hospital, 11528 Athens, Greece.

出版信息

Int J Mol Sci. 2025 Jun 22;26(13):5989. doi: 10.3390/ijms26135989.

Abstract

Pediatric-onset multiple sclerosis (POMS) is a rare yet increasingly recognized demyelinating disease of the central nervous system, characterized by a highly inflammatory disease course and an elevated relapse rate compared to adult-onset MS (AOMS). Given the unique immunopathogenesis of POMS, recent therapeutic strategies have shifted toward early initiation of high-efficacy disease-modifying therapies (DMTs) to minimize irreversible neurological damage. Among these, B-cell-targeting therapies, particularly anti-CD20 monoclonal antibodies, have shown efficacy in adult MS and are emerging as promising candidates for POMS treatment. The present review summarizes the current knowledge of the role of B-cells in POMS pathophysiology and evaluates the therapeutic potential of anti-CD-20 agents. It also highlights ongoing clinical trials and future perspectives, including novel B-cell-directed approaches such as anti-CD19 therapies, Bruton's tyrosine kinase (BTK) inhibitors, and BAFF-targeting agents.

摘要

儿童期多发性硬化症(POMS)是一种罕见但日益受到认可的中枢神经系统脱髓鞘疾病,其特征是与成人期多发性硬化症(AOMS)相比,疾病进程具有高度炎症性且复发率较高。鉴于POMS独特的免疫发病机制,近期的治疗策略已转向早期启动高效疾病修正疗法(DMTs),以尽量减少不可逆的神经损伤。其中,针对B细胞的疗法,特别是抗CD20单克隆抗体,已在成人多发性硬化症中显示出疗效,并正成为POMS治疗的有希望候选药物。本综述总结了目前关于B细胞在POMS病理生理学中的作用的知识,并评估了抗CD20药物的治疗潜力。它还强调了正在进行的临床试验和未来前景,包括新型B细胞导向方法,如抗CD19疗法、布鲁顿酪氨酸激酶(BTK)抑制剂和BAFF靶向药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2999/12250533/3d6e77fb6a4e/ijms-26-05989-g001.jpg

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